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The strike took place in the restive Datta Khel region, 25 kilometres west of Miranshah.
"A US drone fired missiles on a house used by militants, killing three of them," a senior security official told AFP.
Another official also confirmed the missile strike and casualties.
It was not immediately clear if there any high-value targets at the compound at the time of the attack.
"Identities of those killed in the strike also could not be immediately known", the official said.